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Article from the Symposium
Role of endothelin-1 in osteoblastic bone metastases
Article first published online: 23 JAN 2003
Copyright © 2003 American Cancer Society
Supplement: Skeletal Complications of Malignancy
Volume 97, Issue Supplement 3, pages 779–784, 1 February 2003
How to Cite
Guise, T. A., Yin, J. J. and Mohammad, K. S. (2003), Role of endothelin-1 in osteoblastic bone metastases. Cancer, 97: 779–784. doi: 10.1002/cncr.11129
- Issue published online: 23 JAN 2003
- Article first published online: 23 JAN 2003
- Manuscript Accepted: 1 NOV 2002
- Manuscript Received: 15 JUL 2002
- National Institutes of Health. Grant Numbers: CA69158, CA40035
- Department of Defense, U.S. Army. Grant Number: DAMD17-99-1-9401
- bone metastasis;
- breast cancer;
- prostate cancer
Certain solid tumors metastasize to bone and cause an osteoblastic response. The mechanisms by which tumor cells stimulate this new bone formation are not completely understood.
The authors identified three breast cancer lines that cause osteoblastic metastases in female nude mice and provided evidence that tumor-produced endothelin-1 (ET-1) mediates the osteoblastic response.
Tumor conditioned media, as well as exogenous ET-1, stimulated osteoblast proliferation and new bone formation in cultures of mouse calvariae. These effects were blocked by antagonists of the endothelin A (ETA), but not ETB, receptors. Mice inoculated with the ZR-75-1 breast cancer line and treated with a selective ETA receptor antagonist (ABT-627) had significantly fewer osteoblastic bone metastases and less tumor burden compared with untreated mice. In contrast, there was no effect of ABT-627 on osteolytic bone metastases caused by ET-1-negative breast cancer, MDA-MB-231. ABT-627 had no effect on growth in vitro or at the orthotopic site of ZR-75-1 or MDA-MB-231 cells.
Collectively, the data suggested that tumor-produced ET-1 mediates osteoblastic bone metastases by stimulating osteoblast proliferation and new bone formation. ETA receptor blockade may be useful for prevention and the treatment of osteoblastic bone metastases due to breast or prostate cancer. Cancer 2003;97(3 Suppl):779–84. © 2003 American Cancer Society.